Glandular kallikrein is a 'tryptic-like' regulatory serine protease whic is found in a wide variety of tissue and biological fluids including urine, blood and saliva. Although a specific physiological function for this enzyme has not been rigorously established, it has been suggested to be involved in blood pressure regulation, the control of sodium transport, regulation of smooth muscle contraction independent of kinin formation and the processing of peptide hormones. The kallikrein activity found in human saliva is of the glandular kallikrein type and appears to be a product of both submandibular and parotid gland secretion. Although a role in oral pathophysiology has not been identified, several studies suggest that the secretion of this enzyme into saliva can be influenced by systemic physiology and, hence, changes in the concentration of glandular kallikrein in saliva might be an important monitor of specific disease processes. In addition, the source of systemic glandular kallikrein has not been identified but there is evidence obtained in animal model systems which suggest that the salivary glands might be responsible for the glandular kallikrein found in the circulation. The research proposed in this application is focused toward the following questions: (1) What factors influence glandular kallikrein levels in mixed saliva obtained from a normal population; (2) Can the concentration of glandular kallikrein in mixed saliva provide an meaningful index of metastatic disease and what is the effect of oncology therapy on the elevated levels of glandular kallikrein in mixed saliva obtained from subjects with solid tumors distant from the oral cavity; and (3) Are salivary glands a major source of the glandular kallikrein found in blood. This information obtained from these studies will not only provide insight into the source of glandular kallikrein available for systemic action but also will provide background information necessary for using changes in salivary levels of glandular kallikrein to identify and monitor specific changes in systemic pathophysiology.